Aromatic bromination process

ABSTRACT

Aromatic substrates such as benzene, substituted benzenes, naphthalenes, substituted naphthalenes, anthracene, phenanthrene, fluorene, biphenylene, and terphenyl are brominated to give pure monobromo products by reaction with bromine in the presence of thallic acetate.

United States Patent Taylor et al. Sept.5, 1972 [54] AROMATICBROMINATION PROCESS [72] Inventors: Edward C. Taylor; Alexander [56]References C'ted McKillop, both of 1500 Spring H Garden St.,Philadelphia, Pa. 19101 b h OT ER PUBLICATIONS Filed: March 1971 Kab e,C em. Abst. 58, 13760 (1963).

[21] Appl. No.2 125,895 Primary ExaminerLorraine A. Weinberger AssistantExaminer.l0hn F. Tenapane Related Apllhcahon Data Attorney-William l-l.Edgerton et a1. [62] Division of Ser. No. 766,002, Oct. 8, 1968, Pat.

No. 3,622,640. 7] ABSTRACT Aromatic substrates such as benzene,substituted [52] Cl "260/562 260/473 260/562 benzenes, naphthalenes,substituted naphthalenes, 260/577 260/600, 260/609 260/612 anthracene,phenanthrene, fluorene, biphenylene, and 260/613 260/646 terphenyl arebrominated to give pure monobromo [51] Int. Cl ..C07C 103/34 products byreaction with bromine in the presence of [58] Field ofSearch.....260/649, 649 PP, 649 F, 650, thamc acetam 260/650 F, 646,600, 612 D, 613 D, 473 R, 604 D, 577, 562

7 Claims, No Drawings AROMATIC BROMINATION PROCESS This application is adivision of application Ser. No. 766,002, filed Oct. 8, 1968, now US.Pat. No. 3,622,640.

This invention relates to a process for brominating aromatic substances.in particular, the invention relates to a process for brominatingbenzene ring compounds with bromine in the presence of thallic acetate.

The present process constitutes a rapid and convenient method ofobtaining pure brominated aromatic compounds in high yield. Its otheradvances include mildness of reaction conditions, lack ofpolysubstitution, and ease of work-up. It is particularly applicable tocarbocyclic compounds including benzene; substituted benzenes;naphthalene; substituted naphthalenes; and polycyclic aromatic compoundssuch as anthracene, phenanthrene, fluorene, biphenylene, andp-terphenyl. The process is especially advantageous in cases wherebromination by other methods is extremely difficult or requires specialtechniques; biphenylene, anthracene, and fluorene are examples of suchsubstrates. The most important advantage of the present process is thespecificity of reaction. In contrast to the vast majority ofelectrophilic halogenation reactions, application of the present processto substituted benzenoid compounds results in the formation of a singlepure monobromo isomer. The process may also be applicable to thebromination of heterocyclic aromatic substrates.

The substituents on the aromatic nucleus to be brominated may be, butare not necessarily limited to, alkoxy, alkylthio, alkylamino,dialkylamino, acylamino, alkyl, nitro, halo, and carbalkoxy. The termsalkyl and acyl are intended to include lower alkyl or lower acyl groupscontaining up to about six carbon atoms.

When moderately reactive aromatic substrates are brominated, dry bromineisadded to a mixture of the aromatic substrate and thallic acetate in asuitable organic solvent. The molar amounts of substrate and bromine areapproximately equal, and about three times that of the thallic acetate.When the bromine addition has been completed, it is desirable to heatthe mixture, conveniently at reflux, for a short period of time;one-half hour is suitable. The temperature and heating time are notcritical, the end-point of the reaction being observed by thedisappearance from the mixture of the bromine color. Lower temperaturesnecessitate longer reaction times. Generally, the reaction can beconducted over a temperature range of to the reflux temperature of thesolvent. Suitable solvents for the reaction include carbontetrachloride, nitromethane, acetic acid, chloroform, anddichloroethane. When the reaction is completed, the product is obtainedaccording to conventional work-up procedure; conveniently, the inorganicthallium byproducts are filtered off, the filtrate washed with aqueoussodium bicarbonate solution, dried and removed, and the residual productpurified by chromatography on alumina and distillation orcrystallization.

Highly reactive substrates or those in which sidechain bromination mayoccur, are brominated at approximately 0C. When a haloaromatic substrateis brominated, it may be used in excess as the reaction solvent.

, variety of known uses in industry or in organic synthesis. Asexamples, bromobenzene is used as a motor oil additive andbromonaphthalene is used in spectroscopy and refractometry.

The following examples are intended to illustrate the process of theinvention, but are not to be construed as limiting its scope. Variousmodifications in the reactants and conditions of the process are obviousand will occur to those skilled in the art of organic chemistry.

They are to be considered equivalent to the invention and are within itsscope.

EXAMPLE 1 A mixture of 10.8 g. (0.1 mole) of anisole and l 1.43 g. (0.03mole) of thallic acetate in 100 ml. of carbon tetrachloride is stirredunder nitrogen, and a solution of 16.0 g. (0.1 mole) of dry bromine in30 ml. of carbon tetrachloride added at such a rate that no free bromineis present at any time. When addition of bromine has been completed, themixture is refluxed for one-half hour, the hot reaction mixture filteredthrough a sintered funnel to remove the inorganic thallium products, andthe filtrate washed with aqueous NaHCO solution and dried over anhydrousNa SO The solvent is removed under reduced pressure, the residuedissolved in chloroform, and the solution filtered through a shortcolumn of alumina, using chloroform as eluent. Removal of the solventand distillation gives 4- bromoanisole in 91 percent yield.

EXAMPLE 2 When the following aromatic substrates are brominatedaccording to the procedure of Example 1, the corresponding listedproducts are obtained.

Substrate Product Yield N,N-dimethylaniline 4-Bromo-N,N-dimethylanilineN-Methylaniline 4-Bromo-N-methylaniline 60 Thioanisole4-bromothioanisole 73 Benzene Bromobenzene Acetanilide4-Bromoacetanilide 95 Biphenyl 4-Bromobiphenyl 93 Z-Nitrobiphenyl4'-Br0rno-2-nitr0biphenyl 70 l,2-dimethoxybenzene 4-Bromo-l,Z-dimethoxybenzene 85 1,3-dimethoxygenzene 4-Bromol ,S-dimethoxybenzene87 l ,Z-dimethylbenzene 4-Bromo-l ,Z-dimethylbenzene 85l,3-Dimethylbenzene 4-Bromol ,B-dimethylbenzene 8 8 l,4-dimethylbenzene2-Bromol ,4-dimethylbenzene 76 4-Methoxybenzal- 2-Bromo-4-methoxybenzal-66 dehyde dehyde Z-Nitroanisole 2-Nitro-4-bromoanisole 90 S-Nitroanisole3-Nitro-4-bromoanisole 60 4-Nitroanisole 2-Bromo-4-nitroanisole Methylanisate Methyl 2-bromo anisate 90 Methyl 3-methoxy- Methyl 3-methoxy-4-93 benzoate bromobenzoate Methyl Z-methoxy Methyl 2-methoxy-5- 90benzoate bromobenzoate Naphthalene l-Bromonaphthalene 7ll-Methylnaphthalene l-Methyl-4-bromonaphthalene 84 l-Methoxynaphthalenel-Methoxy-4-bromonaphthalene 70 Z-Methoxynaphthalenel-Bromo-2-methoxynaphthalene 68 l-Nitronaphthalenel-Nitro-S-bromonaphthalene 75 Anthracene 9-Bromoanthracene 89Phenanthrene 9-Bromophenanthrene 78 Fluorene 2-Bromofluorene 96Biphenylene Z-Bromobiphenylene 88 p-Terphenyl 4-Bromo-p-terphenyl 80EXAMPLE 3 The following procedure is best applied to those substrateswhich are highly reactive. Such substrates include alkylated benzenes,naphthalenes, and other polycyclic hydrocarbons, including ethylbenzene,propylbenzene, and isopropylbenzene, etc.

Thallic acetate and bromine, in the same molar proportions as in Example1, are mixed together in carbon tetrachloride and cooled to C.Ethylbenzene is then added dropwise over a 15 minute period. Stirring iscontinued for another 15 minutes and the mixture is then worked up as inExample 1 to give 4-bromoethylbenzene (60 percent).

EXAMPLE 4 When the substrate is a halo aromatic compound, the followingprocedure may be used:

To a mixture of 11.43 g. (0.03 mole) of thallic acetate in 100 ml. ofchlorobenzene under nitrogen is added 16.0 g. (0.1 mole) of dry bromine.The reaction mixture is gently heated as bromine is added and theheating is discontinued when the bromine color has begun to bedischarged (a few minutes). The product (4-bromochlorobenzene) isobtained in 70 percent yield by filtering off the thallium residue anddistilling the filtrate.

Other substrates brominated according to this procedure includefluorobenzene (gave 4- bromofluorobenzene in 70 percent yield),bromobenzene (gave p-dibromobenzene in 73 percent yield), andiodobenzene (gave 4-bromoidobenzene in 69 percent yield).

We claim:

1. A process for brominating the aromatic nucleus of a carbocyclicaromatic compound selected from the group consisting of an alkoxy,alkylthio, alkylamino, dialkylamino, lower alkanoylamino, nitro, orcarbalkoxy substituted aromatic hydrocarbon comprising reacting togetherin an organic solvent capable of solubilizing the reactants, at atemperature of from 0C to the boiling point of the solvent, equimolarquantities of bromine and the aromatic compound in the presence ofone-third of a molar equivalent of thallic acetate.

2. A process according to claim 1, in which the aromatic compound isanisole, N,N-dimethylaniline, N- methylaniline, thioanisole,acetanilide, 2-nitrobiphenyl, 1,2-dimethoxybenzene,1,3-dimethoxybenzene, 4- methoxybenzaldehyde, Z-nitroanisole,3-nitroanisole,

4-nitroanisole, methyl anisate, methyl 3-methoxybenzoate, methyl2-methoxybenzoate, l-methoxynaphthalene, 2-methoxynaphthalene, or 1nitronaphthalene.

3. A process according to claim 2, in which the aromatic compound isN,N-dimethylaniline.

4. A process according to claim 2, in which the aromatic compound isanisole.

5. A process according to claim 2, in which the aromatic compound isacetanilide.

6. A process according to claim 2, in which the aromatic compound is1,2-dimethoxybenzene.

7. A process according to claim 2, in which the aromatic compound is4-nitroanisole.

2. A process according to claim 1, in which the aromatic compound isanisole, N,N-dimethylaniline, N-methylaniline, thioanisole, acetanilide,2-nitrobiphenyl, 1,2-dimethoxybenzene, 1,3-dimethoxybenzene,4-methoxybenzaldehyde, 2-nitroanisole, 3-nitroanisole, 4-nitroanisole,methyl anisate, methyl 3-methoxybenzoate, methyl 2-methoxybenzoate,1-methoxynaphthalene, 2-methoxynaphthalene, or 1-nitronaphthalene.
 3. Aprocess according to claim 2, in which the aromatic compound isN,N-dimethylaniline.
 4. A process according to claim 2, in which thearomatic compound is anisole.
 5. A process according to claim 2, inwhich the aromatic compound is acetanilide.
 6. A process according toclaim 2, in which the aromatic compound is 1,2-dimethoxybenzene.
 7. Aprocess according to claim 2, in which the aromatic compound is4-nitroanisole.